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ID PMID Title PublicationDate abstract
21239759 Incidence and mortality of treated primary Sjogren's syndrome in Taiwan: a population-base 2011 Apr OBJECTIVE: To estimate the incidence and mortality of treated primary Sjögren's syndrome (pSS) by sex and age group in Taiwan. METHODS: We used claims data of the Bureau of National Health Insurance (NHI) of Taiwan from 2005 to 2007 for analysis. According to the NHI, pSS is classified as one of the financially catastrophic illnesses and patients with pSS could be exempted from copayment of all medical costs. To obtain a catastrophic illness certificate (CIC) for pSS, patients are required to meet the criteria of the American-European Consensus Group for pSS, and are reviewed by a committee. Patients approved for receipt of a CIC for pSS for the first time were defined as incident cases of treated pSS. RESULTS: A total of 3352 incident cases occurred between 2005 and 2007. The estimated mean annual incidence was 6.0 per 100,000 inhabitants (95% CI 5.8-6.2) for both sexes, 11.0 (95% CI 10.6-11.4) for women and 1.1 (95% CI 1.0-1.2) for men, with a female/male ratio of 9.9 (95% CI 8.8-11.1). Incidence increased with age, peaking at age 55-64 years in women and 65-74 years in men. The mortality rate was 33.4 per 1000 case person-years for men and 11.4 for women, with a male/female rate ratio of 2.9 (95% CI 1.7-5.3). CONCLUSION: The incidence of treated pSS in women is 10 times that in men. Nevertheless, pSS mortality in men is 3 times that in women.
21672284 Sjögren's syndrome: studying the disease in mice. 2011 Jun 13 Sjögren's syndrome (SS), a systemic autoimmune disease, is characterized by inflammation of exocrine tissues accompanied by a significant loss of their secretory function. Clinical symptoms develop late and there are no diagnostic tests enabling early diagnosis of SS. Thus, particularly to study these covert stages, researchers turn to studying animal models where mice provide great freedom for genetic manipulation and testing the effect of experimental intervention. The present review summarizes current literature pertaining to both spontaneous and extrinsic-factor induced SS-like diseases in mouse models, discussing advantages and disadvantages related to the use of murine models in SS research.
21915034 The evolution of histopathologic findings in adult Still disease. 2011 Oct Adult Still disease is an inflammatory arthritis classically associated with daily spiking fevers, evanescent rash, organomegaly, lymphadenopathy, and laboratory anomalies. The typical cutaneous lesions are thin pink papules in a morbilliform distribution, of short duration. Histologically, these lesions are characterized by a superficial perivascular and interstitial mixed dermatitis with lymphocytes and variable neutrophils. A variant clinical presentation is increasingly recognized, which demonstrates persistent hyperpigmented plaques, often with a rippled or linear appearance. The histologic findings consist of upper epidermal dyskeratotic keratinocytes, increased dermal mucin, and a superficial perivascular infiltrate of lymphocytes and possibly neutrophils or eosinophils. We encountered 2 patients who presented with the characteristic rash of adult Still disease, both of whom progressed to develop the pigmented cutaneous plaques. We propose that this variant clinical and histologic appearance is the outcome of persistent disease activity.
22184654 Recurrent parotitis as a presentation of primary pediatric Sjögren syndrome. 2012 Jan Parotitis is a common condition seen in the pediatric population, usually as an isolated occurrence associated with viral or bacterial infection. The differential diagnosis expands when recurrent parotitis is encountered. One etiology is primary pediatric Sjögren syndrome (SS), an autoimmune condition typically associated with dryness of the eyes and mouth in adults. Pediatric patients often present with isolated recurrent bilateral parotitis, however, and we describe 4 such cases in children aged 9 to 17 years at presentation. Despite lack of ocular complaints, 3 of these patients had ocular findings on ophthalmologic exam. Our patients also exhibited classic laboratory abnormalities, including positive antinuclear antibody, SS A, and SS B antibodies; presence of rheumatoid factor; and hypergammaglobulinemia. Consideration of SS in the child with recurrent parotitis is important for timely and appropriate referral and treatment. We review the differential diagnosis of parotitis in children as well as the salient features of pediatric SS.
21785958 Urticaria and dermographism in patients with adult-onset Still's disease. 2012 Aug Adult-onset Still's disease (AOSD) patients typically present with arthralgia, fever, lymphadenopathy and a transient salmon maculopapular rash. Only approximately 25 cases of AOSD with urticaria were described in the literature. In this article, the authors report three additional cases of AOSD with urticarial and dermographic lesions who had a good clinical response to glucocorticoid and antihistamines. A review of the literature concerning this issue is also herein written.
22275833 Investigation of nano lipid vesicles of methotrexate for anti-rheumatoid activity. 2012 BACKGROUND: The purpose of this study was to formulate and evaluate nano lipid vesicles of methotrexate (MTX) for its anti-rheumatoid activity. METHODS: In this study the principle of both active as well as passive targeting using MTX-loaded stealth liposomes as per the magic gun approach was followed. Stealth liposomes of MTX were prepared by thin-film hydration method using a PEGylated phospholipid-like DSPE-MPEG 2000. Similarly, conventional liposomes were prepared using phospholipids like DPPC and DSPC. Conventional liposomes were coated with a hydrophilic biocompatible polymer like chitosan. They were investigated for their physical properties and in vitro release profile. Further, in vivo screening of the formulations for their anti-rheumatoid efficacy was carried out in rats. Rheumatoid arthritis was induced in male Wistar-Lewis rats using complete Freund's adjuvant (1 mg/mL Mycobacterium tuberculosis, heat killed in mineral oil). RESULTS: It was found that chitosan coating of the conventional liposomes increased the physical stability of the liposomal suspension as well as its entrapment efficiency. The size of the unsonicated lipid vesicles was found to be in the range of 8-10 μm, and the sonicated lipid vesicles in the range of 210-260 nm, with good polydispersity index. Further, chitosan-coated conventional liposomes and the PEGylated liposomes released the drug for a prolonged period of time, compared to the uncoated conventional liposomes. It was found that there was a significant reduction in edema volume in the rat group administered with the test stealth liposomal formulations and chitosan-coated conventional liposomes (PEGylated and chitosan-coated conventional) compared to that of the control and standard (administered with free MTX) group of rats. PEGylated liposomes showed almost equal efficacy as that of the chitosan-coated conventional liposomes. CONCLUSION: Lipid nano vesicles of MTX can be administered by intravenous route, whereby the drug selectively reaches the target site with reduced toxicity to other organs.
21711083 Analgesic and anti-inflammatory effects of ethyl acetate fraction of Polygonum cuspidatum 2012 Apr Polygonum cuspidatum (PC) has been used for the treatment of arthritis and urinary diseases in traditional medicine. Despite recent evidence that PC has anti-oxidant, anti-tumoral, and anti-inflammatory effects, analgesic and anti-inflammatory effects of PC have not been elucidated yet in vivo. Thus, in the present study, analgesic and anti-inflammatory effects of ethyl acetate extract of PC (EAPC) were investigated in vivo for the first time. Hot plate test and tail-flick test revealed that EAPC at 200 mg/kg exerts analgesic effect (p < 0.05). In contrast, EAPC did not show significant analgesic effect in acetic acid-induced writhing test. Serotonin-induced paw edema model and Freund's complete adjuvant (FCA)-induced adjuvant arthritis model were used to examine anti-inflammatory effect of EAPC in vivo. In serotonin-induced paw edema model, EAPC suppressed swelling inflammatory response within 12 min after serotonin injection, at both 100- and 200-mg/kg dose (p < 0.05). Consistently, in FCA-induced adjuvant arthritis model, FCA at 200 mg/kg significantly suppressed FCA-induced joint swelling within 3 days (p < 0.05), whereas FCA at 100 mg/kg showed the similar result within 5 days (p < 0.05). Furthermore, EAPC effectively inhibited positive responses of c-reactive protein and rheumatoid factor compared to untreated control. Taken together, our findings suggest that EAPC can be a potent candidate for rheumatoid arthritis treatment.
22970613 [Update on current care guidelines: psoriasis and psoriatic arthritis]. 2012 Psoriasis is a chronic, immune-mediated, inflammatory disorder of the skin and joints. Moderate-to-severe cases are associated with an independent risk of comorbidity (cardiovascular diseases and diabetes) even after adjusting for risk factors, known to be more prevalent in psoriatics compared to normal population. The underlying systemic inflammation, analogous to that observed in rheumatoid arthritis, calls for a long-term effective treatment. Screening and treatment of cardiovascular risk factors is highly recommended. The biologic drug arsenal has new additions. Long term treatment data from clinical study extensions and independent registries are reviewed.
22747898 Statins: a revised appraisal for potential additional future treatment indications. 2012 Jun 29 Beside statins' well established positive influence on atherosclerotic vascular disease caused by hypercholesterolemia through selective competitive inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, additional effects on the immune system have been described for them. These observations have raised great hopes for additional future treatment indications, including rheumatoid arthritis and multiple sclerosis. Ten years of searching for such novel treatment indications have not led to breakthroughs and future efforts must be seen with skepticism.
21468289 Informative value of Patient Reported Outcomes (PRO) in Health Technology Assessment (HTA) 2011 Feb 2 BACKGROUND: "Patient-Reported Outcome" (PRO) is used as an umbrella term for different concepts for measuring subjectively perceived health status e. g. as treatment effects. Their common characteristic is, that the appraisal of the health status is reported by the patient himself. In order to describe the informative value of PRO in Health Technology Assessment (HTA) first an overview of concepts, classifications and methods of measurement is given. The overview is complemented by an empirical analysis of clinical trials and HTA-reports on rheumatoid arthritis and breast cancer in order to report on type, frequency and consequences of PRO used in these documents. METHODS: For both issues systematic reviews of the literature have been performed. The search for methodological literature covers the publication period from 1990 to 2009, the search for clinical trials of rheumatoid arthritis and breast cancer covers the period 2005 to 2009. Both searches were performed in the medical databases of the German Institute of Medical Documentation and Information (DIMDI). The search for HTA-reports and methodological papers of HTA-agencies was performed in the CRD-Databases (CRD = Centre for Reviews and Dissemination) and by handsearching the websites of INAHTA member agencies (INAHTA = International Network of Agencies for Health Technology Assessment). For all issues specific inclusion and exclusion criteria were defined. The methodological quality of randomized controlled trials (RCT) was assessed by a modified version of the Cochrane Risk of Bias Tool. For the methodological part information extraction from the literature is structured by the report's chapters, for the empirical part data extraction sheets were constructed. All information is summarized in a qualitative manner. RESULTS: Concerning the methodological issues the literature search retrieved 158 documents (87 documents related to definition or classification, 125 documents related to operationalisation of PRO). For the empirical analyses 225 RCT (rheumatoid arthritis: 77; breast cancer: 148) and 40 HTA-reports and method papers were found. The analysis of the methodological literature confirms the role of PRO as an umbrella term for a variety of different concepts. The newest classification system facilitates the description of PRO measures by construct, target population and the method of measurement. Steps of operationalisation involve defining a conceptual framework, instrument development, exploration of measurement properties or, possibly, the modification of existing instruments. Seven out of 59 RCT analysing the effects of antibody therapy for rheumatoid arthritis define PRO as the primary endpoint, 38 trials utilize composite measures (ACR, DAS) and ten trials report clinical or radiological parameters as the primary endpoint. Six out of 123 chemotherapy trials for breast cancer define PRO as the primary endpoint, while 98 trials report clinical endpoints (survival, tumour response, progression) in their primary analyses. Discrepancies in the number of trials result from inaccurate specifications of endpoints in the publications. This distribution is reflected in the HTA-reports: while almost all reports on rheumatoid arthritis refer to PRO, this is only the case in about half of the reports on breast cancer. CONCLUSIONS: As definition and classification of PRO are concerned, coherent concepts are found in the literature. Their operationalisation and implementation must be guided by scientific principles. The type and frequency of PRO used in clinical trials largely depend on the disease analysed. The HTA-community seems to pursue the utilization of PRO proactively - in case of missing data the need for further research is stated.
22085512 [Determining cardiovascular risk in patients with rheumatoid arthritis: waiting for trial 2011 Cardiovascular risk management is clearly indicated in patients with rheumatoid arthritis (RA) today because this risk is comparable to patients with diabetes. Although formal evidence of cardiovascular endpoint trials with statins and/or antihypertensives is lacking in patients with RA, there are no indications that these drugs will have limited effect. In contrast, there is accumulating evidence as to the efficacy of the use of these drugs in RA that is at least comparable to their effects in the general population. All patients with RA should therefore receive cardiovascular risk-management therapy aimed at powerful suppression of the chronic inflammatory process as well as treatment with statins and/or antihypertensives, if indicated. Obviously, monitoring in the clinical setting is necessary to document if such therapy does indeed reduce cardiovascular disease in patients with RA.
23723661 Management of rheumatoid arthritis (Aamavata) using symbiohealth healthcare system. 2012 Oct Rheumatoid Arthritis (RA), according to modern medicine, and Aamavata according to Ayurveda, has an etiological and clinical relationship. Aamavata is a disease complex of which RA is a part. A comparative study of the pathophysiology of this disease by both systems reveals that modern medicine has investigated the mechanism of inflammation and has developed an offense strategy to control it. Ayurveda follows a defense strategy and it focuses its search on the etiological process, where disequilibrium at a higher level of physiology affects the gastrointestinal tract, causing an immune response that results in inflammation. Understanding the pathophysiology of both systems will help the treating physician to institute a dual treatment plan of modern medicine's offense strategy and Ayurvedic medicine's defense strategy at appropriate stages of the disease. Studying the pathophsiology of the two systems also gives insight into the genetic and epigenetic phenomenon in the treatment of disease and opens the doors for groundbreaking research.
22953151 Rheumatoid arthritis and Swine influenza vaccine: a case report. 2012 Rheumatoid arthritis (RA) is the most common chronic inflammatory joint disease. Multiple scientific articles have documented that vaccinations for influenza, MMR, and HBV, to name a few, could be triggers of RA in genetically predisposed individuals. However, there is limited data regarding the association of swine flu vaccine (H1N1) and RA. We report the case of a Mexican American female who developed RA right after vaccination with H1N1 vaccine. Genetically, RA has consistently been associated with an epitope in the third hypervariable region of the HLA-DR β chains, known as the "shared epitope", which is found primarily in DR4 and DR1 regions. The presence of HLA-DRB1 alleles is associated with susceptibility to RA in Mexican Americans. Hence, certain individuals with the presence of the "shared epitope" may develop RA following specific vaccinations. To our knowledge, this is the first reported case of RA following vaccination with the swine flu vaccine.
22937439 Serum cytokine concentrations in a patient with rheumatoid arthritis on etanercept therapy 2011 We report a rheumatoid arthritis patient who was treated with etanercept. Serum levels of tumor-necrosis-factor- (TNF-) alpha, soluble-tumor-necrosis-factor receptor- (sTNFR-) I and -II, interleukin- (IL-) 6, and IL-1 beta were measured by ELISA before and during the course of therapy. While the serum levels of IL-6 and IL-1 beta dropped rapidly following the initiation of therapy, the concentrations of TNF-alpha and sTNFR-II steadily increased to a plateau. Although significant clinical efficacy was observed, etanercept had to be discontinued when after 12 weeks of therapy the patient was found to have pneumocystis pneumonia.
26556001 Development and Evaluation of Dual Cross-Linked Pulsatile Beads for Chronotherapy of Rheum 2013 In the present investigation, pulsatile release beads were prepared by ionic gelation technique. Lornoxicam dual cross-linked beads were prepared by dropping dispersed phase of lornoxicam, pectin, and sodium alginate into the dispersion phase of different concentrations of calcium chloride solution followed by aluminium chloride solution. The formulated beads were further coated by Eudragit L & S 100 in the ratio 1 : 2 w/w in order to achieve desired lag time. In vitro release study showed lag time of 5-8 h before release of lornoxicam from the formulated beads. Thus, formulated dual cross-linked beads when administered at bed time may release lornoxicam when needed most for chronotherapeutics of early morning rheumatoid arthritis attacks in chronic patients.
20429008 Sexual maturation in boys with juvenile rheumatoid arthritis. 2011 Nov This paper aimed to study sexual maturation of boys with juvenile rheumatoid arthritis (JRA) during adolescence. This study was carried out in the Department of Pediatrics, Advanced Pediatrics Center, Post Graduate Institute of Medical Education and Research, Chandigarh, India. A total of 70 boys (between 9 and 17 years of age) diagnosed as cases of JRA comprised the sample for this study. Every child was examined for the development of genitalia as per criteria given by Tanner (Growth at adolescence, 2nd edn, Blackwell, Oxford, 1962) at half-yearly age intervals. However, with regard to development of hair (pubic, axillary and facial) mere presence or absence was noted. Mean (±SD) age of attainment of different stages of genitalia development as well as for eruption of hair was ascertained amongst boys who entered puberty using conventional statistics. Initiation of genitalia development (i.e. appearance of G-2 stage) was earliest among boys with systemic onset JRA (10.8 ± 1.3 years). None of the boys with JRA could attain final stage (G-5) of genitalia development by the age of 17 years, as compared with normal Chandigarh boys who had attained this by 15.2 years. Age of appearance of axillary, pubic, and facial hair was also earlier in systemic onset type of disease as compared with those with pauciarticular and polyarticular JRA. The timing of initiation of sexual maturity in boys with different types of JRA remains variably affected, and appears to experience substantial delay in completion of puberty.
22193222 Arthritic disease is more severe in older rats in a kaolin/carrageenan-induced arthritis m 2012 Dec This study examined in an arthritis animal model whether elderly onset rheumatoid arthritis (EORA) is a more severe disease than younger onset rheumatoid arthritis. Arthritis was induced by injecting 5% kaolin/carrageenan into the left tibiotarsal ankles of 18-month-old and 4-week-old rats. Various parameters were measured to evaluate the arthritic progression of kaolin/carrageenan-induced arthritis in the rats. Immunohistochemical staining of arthritic joints was performed to determine the degree of inflammation in old and young rats. Measurements of ankle volume and thickness, arthritic index, number of squeaks, and the paw pressure test showed the 18-month-old rats had more severe disease than the young rats in a kaolin/carrageenan-induced arthritis model. The degree of inflammation and MMP-1 expression of arthritic joints in old rats was significantly higher than that of young rats based on histological evaluation with hematoxylin and eosin (H&E) staining and immunochemistry. More severe disease symptoms were found in old rats with EORA, but the molecular mechanisms still remain to be elucidated. Understanding the molecular mechanisms will be helpful to develop clinical protocols to efficiently treat patients with EORA, which is difficult to control with current protocols.
22226777 Glucocorticoids in nano-liposomes administered intravenously and subcutaneously to adjuvan 2012 Jun 10 We have previously shown that intravenous (i.v.) treatment with sterically stabilized nano-liposomes (NSSL) actively remote-loaded with the glucocorticoid (GC) methylprednisolone hemisuccinate (NSSL-MPS) or betamethasone hemisuccinate (NSSL-BMS) significantly decreased severity of adjuvant arthritis in Lewis rats (a model of human rheumatoid arthritis) throughout all disease stages. Here, we compared i.v. or subcutaneous (s.c.) weekly treatment with each of the two NSSL-GC to weekly or daily treatment with the free drugs or with the TNF-α antagonists Infliximab and Etanercept. Therapeutic efficacy and effects on the profile of pro-inflammatory (IL-6, TNF-α, and INF-γ) and anti-inflammatory (IL-10 and TGF-β) cytokines in rat sera and splenocyte tissue culture supernatants were compared to those of the liposomal and free drugs. Both s.c. and i.v. NSSL-GC suppressed arthritis significantly, compared to higher doses of the free drugs or to TNF-α antagonists. NSSL-GC also suppressed the secretion of pro-inflammatory cytokines, but did not change the levels of TGF- β. The highly efficacious anti-inflammatory therapeutic feature of these nano-drugs makes them candidates for treatment of human rheumatoid arthritis.
21672457 [New insights in adult Still disease's knowledge]. 2011 Jan INTRODUCTION: Adult Still's Disease has systemic consequences, an inflammatory origin and unknown etiology. Knowledge about this disease is still limited, but some evolution has occurred in the last few years. AIMS: Using a clinical case as example, the purpose of this paper is to review actual knowledge about Adult Still's Disease, giving special relevance to the most recent findings. METHODS: Search in Pubmed and Cochrane database (1970-2009) for the terms Adultonset Still's Disease for all available papers. Those considered clinically and historically relevant were selected. An additional search was done in scientific journals and textbooks and other web sites. The information was analysed, using a clinical case in an atypical age as illustration. RESULTS: Adult Still's Disease as multiple manifestations, being fever, evanescent skin rash and arthralgia the most typical. Laboratorial parameters are inespecific, but high glycosilated ferritin is highly suggestive. Non-steroid anti-inflammatory, corticoids, immunosuppressors, and recent biological agents are used in treatment. CONCLUSION: Being uncommon, actual knowledge about this disease is based in isolated descriptions or very short series. There are no specific guidelines, but diagnostic criteria have been improved in recent years, as have the insights in pathophysiology and therapeutic resources.
21878579 Dosing celecoxib in pediatric patients with juvenile rheumatoid arthritis. 2012 Aug The objective was to derive dosing recommendations for the use of celecoxib in patients with juvenile rheumatoid arthritis (JRA) using pharmacokinetic (PK) and exposure-response data. PK and efficacy data from a randomized, double-blind, 12-week study of celecoxib dosed at 3 and 6 mg/kg twice a day (bid) as an investigational suspension formulation in 152 JRA patients aged 2 to 17 years, PK data from 36 adult RA patients, and relative bioavailability data in healthy adults comparing suspension or capsule sprinkles with the commercial capsule were analyzed. Typical oral clearance (L/h) values were 40% and 24% lower in patients weighing 10 and 25 kg, respectively, compared with a 70-kg patient. Longitudinal, logistic pharmacodynamic models incorporating linear effects of dose/area under the plasma concentration-time curve (AUC) over 0 to 12 hours (AUC(0-12)) suggested that the percentage of responders increased with celecoxib exposure. Systemic exposures (AUC) were similar for the suspension, capsule sprinkles, and intact capsule. Administration of a 50-mg bid capsule (or sprinkles) for patients weighing 10 to 25 kg and 100 mg bid for patients >25 kg was predicted to yield similar exposures and response rates as those observed in the JRA trial. Doses and dosage forms not studied in the JRA trial were approved based on the results of this analysis.